The concept that maternal transcripts govern the physiology of the newly formed embryo is derived from studying non-mammalian organisms with readily accessible oocytes and embryos. The eggs of these organisms usually contain spatially localized proteins and mRNAs, and their embryos become motile and transcriptionally active within hours of fertilization. In contrast, full-grown mammalian oocytes are nonpolar, mammalian embryos do not implant into the uterus until several days after fertilization, and embryonic genome activation occurs a day or more after fertilization. Genomic reprogramming takes place during the oocyte to embryo transition, a process that until now has not been possible to study at a large-scale molecular level in mammals. Our goal is to use the information we derived from the large, representative EST libraries we prepared from mouse oocytes and embryos to explore the mechanisms driving nuclear reprogramming. Timely translation of stored maternal mRNAs provides one mechanism for molecular change in a transcriptionally silent cell. We propose combined computational and molecular approaches to identify cis-elements and their protein partners, which delay translation of maternal mRNAs until oocyte maturation or after fertilization. Retrotransposons may shape and/or inform about the processes that modulate the transcriptional activity of the oocyte and 2-cell embryo. We propose in silico and experimental approaches to explore the effects of retrotransposons on the changing architecture of the embryonic genome.